Analogs and Conjugates of Natural Proline-Arginine-Rich Antimicrobial Peptides: Approaching Practical Use?

Antimicrobial peptides, particularly proline- and arginine-rich cationic antimicrobial peptides (PR-AMPs), attract researchers as compounds that can serve as the basis for new-generation antibacterial drugs. This interest is due to the ability of PR-AMPs to act on antibiotic-resistant bacteria, their unique mechanism of action associated with targeting bacterial ribosomes and inhibiting protein synthesis, a broad spectrum of activity against Gram-negative bacteria, a low rate of bacterial resistance development to PR-AMPs, and the relative ease of modifying their structure. However, the application of PR-AMPs is limited by their proteolytic degradation in biological environments, an insufficiently broad spectrum of activity against Gram-positive bacteria, the potential emergence of bacterial resistance to them, and toxic effects due to the interaction of PR-AMPs with some components of eukaryotic cells. One way to overcome these drawbacks is to change the structure of PR-AMPs through their modification and conjugation with other molecules. The review covers analogs and conjugates of PR-AMPs, information about which has been published in recent years, methods of PR-AMP modification; the new properties of compounds derived from PR-AMPs are analyzed in light of the prospects for creating antibacterial agents.